Superficial siderosis of the central nervous system: secondary progression despite successful surgical treatment, mimicking amyotrophic lateral sclerosis. Case report and review

Superficial siderosis of the central nervous system is a rare disorder with hemosiderin deposition in the spinal and cranial leptomeninges and subpial layer, mostly from repetitive subarachnoid hemorrhage. Progressive sensorineural deafness, cerebellar ataxia, and pyramidal signs comprise the typical clinical presentation. We describe a 47-year-old patient, who showed initial 2-year improvement after successful occlusion of an intradural bleeding source at T4. Secondary progression of symptoms without further bleedings was noted thereafter, with a clinical picture of amyotrophic lateral sclerosis. This case illustrates that the disease may progress secondarily even without re-bleedings, and that secondary progression might be due to a similar pathomechanism as in amyotrophic lateral sclerosi

Multiple Coaxial Catheter System for Reliable Access in Interventional Stroke Therapy

In some patients with acute cerebral vessel occlusion, navigating mechanical thrombectomy systems is difficult due to tortuous anatomy of the aortic arch, carotid arteries, or vertebral arteries. Our purpose was to describe a multiple coaxial catheter system used for mechanical revascularization that helps navigation and manipulations in tortuous vessels. A triple or quadruple coaxial catheter system was built in 28 consecutive cases presenting with acute ischemic stroke. All cases were treated by mechanical thrombectomy with the Penumbra System. In cases of unsuccessful thrombo-aspiration, additional thrombolysis or angioplasty with stent placement was used for improving recanalization. The catheter system consisted of an outermost 8-Fr and an intermediate 6-Fr guiding catheter, containing the inner Penumbra reperfusion catheters. The largest, 4.1-Fr, reperfusion catheter was navigated over a Prowler Select Plus microcatheter. The catheter system provided access to reach the cerebral lesions and provided stability for the mechanically demanding manipulations of thromboaspiration and stent navigation in all cases. Apart from their mechanical role, the specific parts of the system could also provide access to different types of interventions, like carotid stenting through the 8-Fr guiding catheter and intracranial stenting and thrombolysis through the Prowler Select Plus microcatheter. In this series, there were no complications related to the catheter system. In conclusion, building up a triple or quadruple coaxial system proved to be safe and efficient in our experience for the mechanical thrombectomy treatment of acute ischemic strok

Use of the Enterprise™ Intracranial Stent for Revascularization of Large Vessel Occlusions in Acute Stroke

Background and Purpose:: Major cerebral thromboembolism often resists recanalization with currently available techniques. The authors present their initial experience with a self-expanding stent for use in intracranial vascular reconstruction, permitting immediate recanalization of acute thromboembolic occlusions of the anterior circulation. Patients and Methods:: Patients treated with the Cordis Enterprise™ self-expanding intracranial stent system for acute thromboembolic occlusion of the major anterior cerebral arteries were included. Treatment comprised systemic and intraarterial thrombolysis, mechanical thrombectomy, and stent placement. Stent deployment, recanalization rate by means of Thrombolysis In Cerebral Infarction (TICI) scores and the clinical outcome were all assessed. Results:: Six patients presenting with acute carotid T (n = 2) or proximal middle cerebral artery occlusion (n = 4) were treated. The mean National Institutes of Health Stroke Scale (NIHSS) score at presentation was 14; the mean age was 57 years. Successful stent deployment and immediate recanalization were achieved in all six with a TICI score of ≥ 2. Neither distal emboli nor any procedure-related complications were encountered. One patient developed symptomatic intracerebral hemorrhage and two patients needed decompressive craniectomy after treatment. The mean NIHSS score at 10 days was 10, but only one patient showed a complete recovery at 3 months. Conclusion:: Intracranial placement of the Enterprise™ self-expanding stent has proven to be feasible and efficient in achieving immediate recanalization of occluded main cerebral arteries. The use of antiplatelet therapy after treatment may, however, increase the risk of reperfusion intracerebral hemorrhag

Euclid preparation -XIX. Impact of magnification on photometric galaxy clustering

Aims. We investigate the importance of lensing magnification for estimates of galaxy clustering and its cross-correlation with shear for the photometric sample of Euclid. Using updated specifications, we study the impact of lensing magnification on the constraints and the shift in the estimation of the best fitting cosmological parameters that we expect if this effect is neglected. Methods. We follow the prescriptions of the official Euclid Fisher matrix forecast for the photometric galaxy clustering analysis and the combination of photometric clustering and cosmic shear. The slope of the luminosity function (local count slope), which regulates the amplitude of the lensing magnification, and the galaxy bias have been estimated from the Euclid Flagship simulation. Results. We find that magnification significantly affects both the best-fit estimation of cosmological parameters and the constraints in the galaxy clustering analysis of the photometric sample. In particular, including magnification in the analysis reduces the 1σ errors on Ωm, 0, w0, wa at the level of 20–35%, depending on how well we will be able to independently measure the local count slope. In addition, we find that neglecting magnification in the clustering analysis leads to shifts of up to 1.6σ in the best-fit parameters. In the joint analysis of galaxy clustering, cosmic shear, and galaxy–galaxy lensing, magnification does not improve precision, but it leads to an up to 6σ bias if neglected. Therefore, for all models considered in this work, magnification has to be included in the analysis of galaxy clustering and its cross-correlation with the shear signal (3 × 2pt analysis) for an accurate parameter estimation. Key words: large-scale structure of Universe / cosmological parameters / cosmology: theor

Protein–protein HADDocking using exclusively pseudocontact shifts

In order to enhance the structure determination process of macromolecular assemblies by NMR, we have implemented long-range pseudocontact shift (PCS) restraints into the data-driven protein docking package HADDOCK. We demonstrate the efficiency of the method on a synthetic, yet realistic case based on the lanthanide-labeled N-terminal ε domain of the E. coli DNA polymerase III (ε186) in complex with the HOT domain. Docking from the bound form of the two partners is swiftly executed (interface RMSDs < 1 Å) even with addition of very large amount of noise, while the conformational changes of the free form still present some challenges (interface RMSDs in a 3.1–3.9 Å range for the ten lowest energy complexes). Finally, using exclusively PCS as experimental information, we determine the structure of ε186 in complex with the HOT-homologue θ subunit of the E. coli DNA polymerase III

Twin gradients in APOBEC3 edited HIV-1 DNA reflect the dynamics of lentiviral replication

The human immunodeficiency virus (HIV) Vif protein blocks incorporation of two host cell cytidine deaminases, APOBEC3F and 3G, into the budding virion. Not surprisingly, on a vif background nascent minus strand DNA can be extensively edited leaving multiple uracil residues. Editing occurs preferentially in the context of TC (GA on the plus strand) and CC (GG) depending on the enzyme. To explore the distribution of APOBEC3F and –3G editing across the genome, a product/substrate ratio (AA + AG)/(GA + GG) was computed for a series of 30 edited genomes present in the data bases. Two highly polarized gradients were noted each with maxima just 5′ to the central polypurine tract (cPPT) and LTR proximal polypurine tract (3′PPT). The gradients are in remarkable agreement with the time the minus strand DNA remains single stranded. In vitro analyses of APOBEC3G deamination of nascent cDNA spanning the two PPTs showed no pronounced dependence on the PPT RNA:DNA heteroduplex ruling out the competing hypothesis of a PPT orientation effect. The degree of hypermutation varied smoothly among genomes indicating that the number of APOBEC3 molecules packaged varied considerably

Carotid plaque surface echogenicity predicts cerebrovascular events: An Echographic Multicentric Swiss Study.

BACKGROUND AND PURPOSE To determine the prognostic value for ischemic stroke or transitory ischemic attack (TIA) of plaque surface echogenicity alone or combined to degree of stenosis in a Swiss multicenter cohort METHODS: Patients with ≥60% asymptomatic or ≥50% symptomatic carotid stenosis were included. Grey-scale based colour mapping was obtained of the whole plaque and of its surface defined as the regions between the lumen and respectively 0-0.5, 0-1, 0-1.5, and 0-2 mm of the outer border of the plaque. Red, yellow and green colour represented low, intermediate or high echogenicity. Proportion of red color on surface (PRCS) reflecting low echogenictiy was considered alone or combined to degree of stenosis (Risk index, RI). RESULTS We included 205 asymptomatic and 54 symptomatic patients. During follow-up (median/mean 24/27.7 months) 27 patients experienced stroke or TIA. In the asymptomatic group, RI ≥0.25 and PRCS ≥79% predicted stroke or TIA with a hazard ratio (HR) of respectively 8.7 p = 0.0001 and 10.2 p < 0.0001. In the symptomatic group RI ≥0.25 and PRCS ≥81% predicted stroke or TIA occurrence with a HR of respectively 6.1 p = 0.006 and 8.9 p = 0.001. The best surface parameter was located at 0-0.5mm. Among variables including age, sex, degree of stenosis, stenosis progression, RI, PRCS, grey median scale values and clinical baseline status, only PRCS independently prognosticated stroke (p = 0.005). CONCLUSION In this pilot study including patients with at least moderate degree of carotid stenosis, PRCS (0-0.5mm) alone or combined to degree of stenosis strongly predicted occurrence of subsequent cerebrovascular events

Central Retinal Artery Occlusion: Current Practice, Awareness and Prehospital Delays in Switzerland

BACKGROUND AND PURPOSE: Central retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO. METHODS: (1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland. RESULTS: Three hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy. CONCLUSIONS: CRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p &lt; 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. METHODS We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). RESULTS We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). CONCLUSIONS Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage